Panitumumab Injection (Vectibix™)
Pharmacology Update
Panitumumab Injection (Vectibix™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
Panitumumab is a human monoclonal antibody that is approved for the treatment of colorectal carcinoma. The drug binds to the human epidermal growth factor receptor (EGFR) in a way similar to cetuximab, which is a chimeric antibody (part mouse part human). Panitumumab is marketed by Amgen as Vectibix.
Indications
Panitumumab is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimdine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.1
Dosage
The recommended dose of panitumumab is 6 mg/kg, given over 60 minutes as an intravenous infusion, every 14 days. Doses higher than 1000 mg should be given over 90 minutes.1
Potential Advantages
Panitumumab prolongs progression-free survival by about 1 month (96 days vs 60 days) in patients with metastatic carcinoma of the colon or rectum.1,3 Panitumumab is a fully human monoclonal antibody. It has been associated with less infusion-related reactions and a lower antibody formation against the drug than cetuximab, 1% vs. 3%.2,3 Compared to cetuximab, panitumumab does not require premedication (eg, intravenous diphenhydramine).3
Potential Disadvantages
It is not certain if panitumumab improves overall survival compared to best supportive care (BSC).1 Severe dermatologic toxicities have been reported in 12% of patients and severe infusion reactions in 1% of patients.1 Other adverse events include fatigue, abdominal pain, paronychia, nausea, diarrhea, constipation, vomiting, and hypomagnesemia.4
Comments
Panitumumab is a fully humanized monoclonal antibody with high selectivity for EGFR (both normal and tumor cells). EGFR is overexpressed in 25-77% of colorectal cancers and is generally associated with poor prognosis. The efficacy of panitumumab was shown in an open-label, multinational, randomized controlled trial of 463 patients with EGFR-expressing metastatic carcinoma of the colon or rectum. Seventy-five percent had progressed on or followed a regimen(s) containing a fluoropyrimidine, oxaliplatin, and irinotecan.1 Patients were randomized to panitumumab (6 mg/kg every 2 weeks or 2.5 mg/kg/week) plus BSC or BSC alone. Mean progression-free survival was 96 days for panitumumab and 60 days for BSC. Progressive free survival rates were 49% vs 30% at week 8, 18% vs 5% at week 24, 10% vs 4% at week 32, and 1% each at week 48.4 There was no difference in overall survival; however, this may be misleading as 75% of those randomized to BSC were allowed to receive panitumumab. The median time to crossover was 8.4 weeks.1,3 Dermatologic toxicities are typically associated with EGFR inhibition (89%) and efficacy and toxicity may be related.5 Nondermatologic adverse events (25%) include fatigue, diarrhea, abdominal pain, constipation, nausea, and hypomagnesemia. The incidence and severity of diarrhea increases when panitumumab is used with irinotecan. Grade 3 or 4 hypomagnesemia occurs in 2% of patients, usually occurring 6 weeks after initiation of therapy. Monitoring of magnesium and calcium levels should be done during and for 8 weeks after therapy. Pulmonary fibrosis has been reported in 2 of 1467 patients. There are currently no comparative trials between panitumumab and cetuximab. However, when studied in similar patients (disease resistant to irinotecan and/or oxaliplatin), both drugs produced response rates of about 10% and stable diseases of 30-40%.5 Panitumumab and cetuximab are currently being studied as first line therapy. The wholesale cost for panitumumab is $800 per 100 mg.
Clinical Implications
Panitumumab is the first fully human monoclonal antibody against EGFR. It provides a better tolerated alternative to cetuximab in patients with metastatic colorectal cancer.
References
1. Vectibix Product Information. Amgen Inc., September 2006.
2. Cohenuram M, et al. Anticancer Drugs. 2007;18(10:7-15.
3. Erbitux Product Information. ImClone Systems Inc. and Bristol-Myers Squibb. March 2006.
4. Hoy S, et al. Drugs. 2006;66(15):2005-2014.
5. Van Cuisem E. Oncologist. 2006;11(9):1010-1017.
Panitumumab is a human monoclonal antibody that is approved for the treatment of colorectal carcinoma.Subscribe Now for Access
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